Clinical trial
A Phase 2, Double-blind, Randomized, Placebo-controlled Study to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol (GWP42003-P)
Name
GWEP1428 Blinded Phase
Description
This trial consists of 2 parts: a double-blinded phase and an open-label extension phase. The blinded phase only will be described in this record. Participants were randomized in a 4:1 ratio to receive GWP42003-P or matching placebo.
Trial arms
Trial start
2016-01-20
Estimated PCD
2016-07-21
Trial end
2016-07-21
Status
Completed
Phase
Early phase I
Treatment
GWP42003-P 20 mg/kg/Day Dose
GWP42003-P was an oral solution containing 25 mg/mL cannabidiol (CBD) or 100 mg/mL CBD dissolved in the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).
Arms:
GWP42003-P 20 mg/kg/Day Dose
Other names:
CBD, Cannabidiol, Epidiolex
Placebo
Placebo oral solution contained the excipients sesame oil and anhydrous ethanol (79 mg/mL) with added sweetener (0.5 mg/mL sucralose) and strawberry flavoring (0.2 mg/mL).
Arms:
Placebo
Clobazam
Participants were already on a stable dose of CLB at Baseline and continued to take a stable dose of CLB for the duration of the blinded phase of the study. CLB was administered either once or twice daily in line with the physician's preferred dosing regimen for the CLB for each participant.
Arms:
GWP42003-P 20 mg/kg/Day Dose, Placebo
Other names:
CLB
Size
20
Primary endpoint
Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of CLB And N-CLB With GWP42003-P Treatment, Days 1 And 33
Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33
PK: Time To The Maximum Plasma Concentration (Tmax) Of CLB And N-CLB With GWP42003-P Treatment, Days 1 And 33
Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33
PK: Area Under The Plasma Concentration-Time Curve Over A Dosing Interval, Where Tau Is The Dosing Interval (AUCtau) Of CLB And N-CLB With GWP42003-P Treatment, Days 1 And 33
Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33
PK: Geometric Mean Ratios Of CLB And N-CLB For Cmax On Day 33 Compared With Day 1
Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33
PK: Geometric Mean Ratios Of CLB And N-CLB For AUCtau On Day 33 Compared With Day 1
Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33
Eligibility criteria
Key Inclusion Criteria:
* Participant must have had epilepsy, as determined by the investigator, and must have been taking CLB.
* Participant must have had a documented magnetic resonance imaging/computerized tomography of the brain ruling out a progressive neurologic condition.
* Participant must have experienced at least 1 seizure of any type (that is, convulsive: tonic-clonic, tonic, clonic, atonic; focal: focal seizures with retained consciousness and a motor component, focal seizures with impaired consciousness, focal seizures evolving to bilateral secondary generalization) within the 2 months prior to randomization.
* Participant must have been taking CLB and no more than 2 other antiepileptic drugs (AEDs) during the course of the trial.
* AED(s), including CLB, must have been stable for 4 weeks prior to screening and regimen must have remained stable throughout the duration of the blinded phase of the trail.
* Intervention with vagus nerve stimulation and/or ketogenic diet must be stable for 4 weeks prior to Baseline and participant/caregiver must have been willing to maintain a stable regimen throughout the blinded phase of the study.
Key Exclusion Criteria:
* Participant had clinically significant unstable medical conditions other than epilepsy.
* Participants were on CLB at doses above 20 mg per day.
* Participants taking CLB intermittently as rescue medication.
* Participant had a history of symptoms related to a drop in blood pressure due to postural changes (for example, dizziness, light-headedness, blurred vision, palpitations, weakness, syncope).
* Participant had any history of suicidal behavior or any suicidal ideation of type 4 or 5 on the Columbia Suicide Severity Rating Scale in the last month or at screening.
* Participant had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to screening or enrollment, other than epilepsy.
* Participant had consumed alcohol during the 7 days prior to enrollment and was unwilling to abstain during the blinded phase of the trail.
* Participant was currently using or has in the past used recreational or medicinal cannabis, or synthetic cannabinoid-based medications (including Sativex®) within the 3 months prior to trial entry.
* Participant had any known or suspected history of any drug abuse or addiction.
* Participant was unwilling to abstain from recreational or medicinal cannabis, or synthetic cannabinoid based medications (including Sativex) for the duration for the study.
* Participant consumed grapefruit or grapefruit juice 7 days prior to enrollment and was unwilling to abstain from drinking grapefruit juice within 7 days of pharmacokinetic visits.
* Participant had any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP, for example, sesame oil.
* Participant received an IMP within the 12 weeks prior to the screening visit.
* Participant had significantly impaired hepatic function at the screening or randomization visit, defined as any of the following:
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 × upper limit of normal (ULN).
* ALT or AST \> 3 × ULN and total bilirubin \> 2 × ULN or international normalized ratio \> 1.5.
* ALT or AST \> 3 × ULN with the presence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (\> 5%).
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 20, 'type': 'ACTUAL'}}
Updated at
2022-09-28
1 organization
Organization
Jazz Pharmaceuticals